Atherosclerosis may result from alterations in lipid metabolism, arterial injury from the effects of chemical or viral mutagens on vascular smooth muscle cells (SMC). Viruses may be inciters of arterial injury or they may alter aortic lipid metabolism. Our previous experiments have shown that occlusive chronic atherosclerosis closely resembling human atherosclerosis can be induced in both normo-and hypercholesterolemic specific-pathogen-free (SPF) chickens by infection with Marek's disease herpesvirus (MDV). Lesions were not found in uninfected controls. These findings may be especially pertinent to human atherosclerosis since man is persistently infected with as many as five herpesviruses. The pathogenesis of these arterial lesions is not well defined. In particular, the mechanism of arterial lipid accumulation in MDV-infected chickens is unclear. Recently, the pathogenesis of MDV-induced atherosclerosis in normocholesterolemic chickens was investigated by assessing lipid accumulation in arteries of infected chickens at 2, 4, and 8 months of age. Preliminary findings indicate that MDV-infection resulted in a significant increase in cholesterol (CH) and cholesteryl ester (CE) by 4-8 months of age as compared to uninfected chickens. These findings parallel our recently completed in vitro studies which showed that MDV-infected SMC accumulate significant quantities of CH and CE as compared to uninfected SMC. Major mechanisms responsible for lipid accretion in these arteries have yet to be elucidated. In this project, I propose to: (1) further indentify and quantitate the types of lipid accumulating in arteries of MDV-infected chicked fed a lipid-poor or cholesterol supplemented diet as compared to their respective uninfected controls; (2) examine the effect of infection with MDV on CE synthesis hydrolysis by assaying activity of acyl CoA: cholesterol acyltransferase (ACAT) as well as acid and neutral CE hydrolase; (3) assess the effects of MDV-infection on cholesterol biosynthesis by examining the activity of HMG-CoA reductase, the key regulatory enzyme in de novo cholesterol synthesis. Results from these experiments should contribute significantly to our understanding of possible mechanisms by which this herpesvirus may induce lipid accretion and atherosclerosis.